In the related art, a liquid collected from an organism or the like is analyzed by a known analyzing method using an analyzing device having fluid channels formed therein. The analyzing device can control a fluid with a rotator. By using a centrifugal force, the analyzing device can dilute a sample liquid, measure a solution, separate a solid component, transfer and distribute a separated fluid, and mix the solution and a reagent, thereby enabling various biochemical analyses.
Patent Literature 1 describes an analyzing device for transferring a solution by a centrifugal force. As shown in FIG. 57, a sample liquid is injected into a storage cavity 92 from an inlet 91 by an inserting instrument such as a pipette, the sample liquid is transferred to a separating cavity 93 and is centrifugally separated therein by rotations of an analyzing device 90, and then solution components are collected into a measuring passage 95 through a connecting passage 94. At the subsequent rotation of the analyzing device 90, solution components in the measuring passage 95 can be transferred to a measurement spot 96. At this point, in order to prevent whole blood retained in the separating cavity 93 from flowing into the connecting passage 94 and the measuring passage 95 thereafter, a siphon-shaped connecting passage 97 for discharging the whole blood is provided on the outermost part of the separating cavity 93. By using the siphon action of the connecting passage 97, an excessive sample liquid in the separating cavity 93 is discharged into an overflow cavity 98.
Patent Literature 2 describes an analyzing device for transferring a solution by using a centrifugal force. As shown in FIG. 58, a diluent measured by a centrifugal force in a diluent measuring chamber 84 and supernatant plasma centrifugally separated in a separating chamber 80 are transferred into a mixing chamber 86 through siphon passages 82 and 84 by a centrifugal force. After agitation in the mixing chamber 86, the solution is transferred to measurement cells 88, which are provided outside the mixing chamber 86, through a siphon passage 87 and is measured therein.
Patent Literature 3 describes an analyzing device for measuring a sample by using a centrifugal force. The analyzing device is configured as shown in FIGS. 59 to 62.
FIG. 59 shows an analyzing device of the invention. FIG. 60 shows a base substrate on which a microchannel is formed as a principle part of the analyzing device.
In FIG. 59, the analyzing device is made up of a base substrate 3 having microchannels 204a and 204b, a cover substrate 4 closing the opening of the base substrate 3, and an adhesive layer 300.
The microchannels 204a and 204b on the base substrate 3 are formed by injection molding the uneven microchannel pattern of FIG. 60. A sample liquid to be analyzed can be injected into the analyzing device and can be moved by a centrifugal force and a capillary force. In FIG. 61, a rotation axis 107 is the center of rotation of the analyzing device in analysis.
In the analyzing device during measurement, the microchannel 204a is filled with a reaction solution 205 in which a sample liquid has reacted with a reagent. The reaction solution 205 fluctuates in absorbance with a ratio of the sample liquid and the reagent. The microchannel 204a is irradiated with light transmitted from a light source 206 and the quantity of the transmitted light is measured on a light receiving section 207, so that a change of light quantity having passed through the reaction solution 205 can be measured to analyze a state of reaction.
The following will describe the microchannel configuration of the analyzing device and the transfer process of the sample liquid.
FIG. 61 is a plan view showing the microchannel configuration of the analyzing device. FIGS. 62(a) to 62(d) show the transfer process of the analyzing device.
As shown in FIGS. 60 and 61, the microchannel configuration includes a liquid storage chamber 209 for injecting and storing the sample liquid; a measuring chamber 210 for measuring a fixed quantity of the sample liquid and retaining the sample liquid therein; an overflow chamber 211 for receiving an excessive sample liquid when the volume of the sample liquid is larger than the capacity of the measuring chamber 210; and a measurement cell 212 that receives the sample liquid measured in the measuring chamber 210, allows the sample liquid to react with the reagent, and measures absorbance.
The liquid storage chamber 209 is connected to the measuring chamber 210 via a connecting passage 213. As shown in FIG. 62(a), the sample liquid is injected and stored in the liquid storage chamber 209 from an inlet 208 and the analyzing device is rotated, so that the sample liquid can be transferred to the measuring chamber 210 as shown in FIG. 62(b).
The measuring chamber 210 is connected to an inlet 216 of the overflow chamber 211 disposed inside the measuring chamber 210 in the radial direction of rotation, from an overflow port 214 at the innermost position of the measuring chamber 210 in the radial direction of rotation via a capillary passage 217. The measuring chamber 210 is connected to the measurement cell 212 from the outermost position of the measuring chamber 210 in the radial direction of rotation via a connecting passage 215. The overflow chamber 211 has an air hole 218 facilitating the passage of the sample liquid. The measurement cell 212 also has an air hole 219 facilitating the passage of the sample liquid through the connecting passage 215.
The connecting passage 215 has a siphon shape and includes a bent pipe disposed between the rotation axis of the analyzing device and the interface between the inlet 216 of the overflow chamber 211 and the capillary passage 217.
The measuring chamber 210 and the measurement cell 212 are connected thus, so that even when the sample liquid stored in the liquid storage chamber 209 is transferred to the measuring chamber 210 by a rotation of the analyzing device, the sample liquid in the connecting passage 215, as shown in FIG. 62(b), reaches only a position corresponding to a distance from the rotation axis of the analyzing device to the interface between the inlet 216 of the overflow chamber 211 and the capillary passage 217 in the radial direction of rotation.
When the analyzing device is stopped after the measuring chamber 210 is filled with the sample liquid, a capillary force is applied in the connecting passage 215. As shown in FIG. 62(c), the sample liquid reaches the inlet of the measurement cell 212. At this point, the measurement cell 212 has a large depth and the capillary force is quite smaller than that of the connecting passage 215, so that the sample liquid does not flow into the measurement cell 212.
After the connecting passage 215 is filled with the sample liquid, the analyzing device is rotated again, so that as shown in FIG. 62(d), the sample liquid retained in the measuring chamber 210 is transferred to the measurement cell 212 by a siphon action.
Of the wall surfaces of the measuring chamber 210, the inner wall surface in the radial direction of rotation of the analyzing device is formed inward in the radial direction of rotation, from a portion around the connecting passage 213 of the measuring chamber 210 toward a portion around the overflow port 214. In other words, of the wall surfaces of the measuring chamber 210, the inner wall surface in the radial direction of rotation of the analyzing device is positioned closer to the rotation axis in the radial direction of rotation, from the sample liquid inlet of the measuring chamber 210 toward the overflow port. Thus when the sample liquid is transferred from the liquid storage chamber 209, air in the measuring chamber 210 is selectively evacuated to the overflow port 214, so that the measurement of the sample liquid is hardly varied by entrained air when the measuring chamber 210 is filled with the sample liquid.
The capillary passage 217 is 50 μm to 200 μm in depth. During a rotation of the analyzing device, a liquid level is stably measured at a position corresponding to a distance to the interface between the inlet 216 of the overflow chamber 211 and the capillary passage 217 in the radial direction of rotation. At the deceleration/stop of a rotation, the sample liquid is trapped in the capillary passage 217 by a capillary force of the capillary passage 217. Thus it is possible to prevent the sample liquid from flowing into the overflow chamber 211 and achieve precise measurement. Further, the sample liquid trapped in the capillary passage 217 is returned to the measuring chamber 210 by a centrifugal force in the subsequent rotation. Thus the measured sample liquid can be fully transferred to the subsequent process.
The sample liquid injected into the liquid storage chamber 209 is transferred to the measuring chamber 210 thus by a rotation of the analyzing device. The sample liquid exceeding a fixed quantity is discharged into the overflow chamber 211 through the capillary passage 217, so that a predetermined quantity of the sample liquid can be measured.
In Patent Literature 4 shown in FIGS. 63(a) and 63(b), a sample liquid is injected into an inlet passage 284 from an inlet 286 by an inserting instrument such as a pipette, the sample liquid is transferred to a measurement cell 285 by a rotation of an analyzing device, the sample liquid is sucked by a capillary force applied to a passage 287 in response to the deceleration or stop of a rotation, and the rotation is accelerated again to return the sample liquid to the measurement cell 285, so that the sample liquid and a reagent 288 can be stirred.